bims-exocan 2026-03-08 papers

Issue of 2026–03–08
three papers selected by
Muhammad Rizwan, COMSATS University

Int J Mol Med. 2026 May;pii: 114. [Epub ahead of print]57(5):

Exosomal circ0000549 promotes MNNG‑induced gastric cancer through miR‑15b‑5p/KIF1B.

Zhaofeng Liang, Zihan Gao, Yue Zhang, Jiajia Song, Hui Qian, Xuezhong Xu.

Accumulating evidence indicates that environmental exposures, particularly to nitrites, play a critical role in the initiation and progression of gastric cancer (GC). During carcinogenesis, exosomes act as key mediators of intercellular communication. Exosomes derived from N‑methyl-N'‑nitro‑N‑nitrosoguanidine (MNNG)‑induced malignantly transformed GES‑1 cells (TGES‑1), as well as serum exosomes from gastric cancer patients with a history of high nitrite exposure, were found to influence normal cells and promote GC initiation. The present study established a malignant transformation model and applied bioinformatics analyses to screen and validate candidate circRNAs. A series of functional and mechanistic experiments were performed to elucidate the regulatory role of exosomes in GC progression. Circ0000549 was markedly upregulated in MNNG‑exposed GES‑1 cells, their derived exosomes and serum exosomes from patients with GC. Further investigations revealed that circ0000549 overexpression enhanced GES‑1 cell malignant features, while also modulating epithelial‑mesenchymal transition and stemness‑related properties. Nude mouse experiments demonstrated that circ0000549, carried by malignantly transformed exosomes, plays a crucial role in MNNG‑induced gastric carcinogenesis. Mechanistically, miR‑15b‑5p was identified as a potential target of circ0000549. Circ0000549 functioned as a sponge for miR‑15b‑5p, leading to increased KIF1B expression and subsequent activation of the PI3K/AKT signaling pathway. Collectively, these findings reveal that exosomal circ0000549 promotes malignant transformation of GES‑1 cells through the miR‑15b‑5p/KIF1B/PI3K/AKT axis. Exosomal circ0000549 may serve as a promising biomarker for GC diagnosis and prognosis, highlighting its potential as a target for future therapeutic investigation.

Keywords: Circ0000549; N‑methyl‑N'‑nitro‑N‑nitrosoguanidine; chemical carcinogenesis; exosome; gastric cancer; microRNA 15b‑5p

DOI: https://doi.org/10.3892/ijmm.2026.5785

Int J Nanomedicine. 2026 ;21 583756

Exosomes as Pivotal Mediators of Tumor-Immune Communication: Implications for Immunotherapy and Liquid Biopsy.

Menglin Wei, Dongli Wang, Wenrong Xu, Xueyan Zang, Jiajia Jiang.

Exosomes are membrane-bound vesicles secreted by almost all types of cells, including but not limited to immune cells, neurons, epithelial cells, and cancer cells. Exosomes carry DNA, RNA, lipids, metabolites, as well as cytoplasmic and cell surface proteins. Their role in cancer progression is dynamic and is related to the type of cancer, genetics, and stage. At the same time, exosomes have attracted widespread attention as key mediators of intercellular communication in the tumor immune microenvironment (TME). This comprehensive review delineates the pleiotropic roles of exosomes in tumor immunobiology, emphasizing their bimodal capacity to either foster immunosuppression or potentiate antitumor immunity. We systematically synthesize recent advancements in exosome-based immunotherapeutic regimens, with particular emphasis on their synergistic efficacy when integrated with established modalities, namely immune checkpoint blockade and adoptive cellular therapy. Furthermore, we critically appraise emergent technologies for exosome isolation and characterization, underscoring their transformative implications for liquid biopsy platforms in real-time immune surveillance and the development of predictive biomarkers. This review posits exosome-centric strategies as a paradigm-shifting frontier in precision immuno-oncology, furnishing innovative remedies for recalcitrant therapeutic hurdles and propelling the advancement of personalized oncology care.

Keywords: biomarker; cancer immunotherapy; exosome; liquid biopsy; tumor immune microenvironment

DOI: https://doi.org/10.2147/IJN.S583756

Cell Signal. 2026 Feb 27. pii: S0898-6568(26)00082-3. [Epub ahead of print]143 112432

Intercellular transfer of circ_0017636 via exosomal vehicles overcomes glioblastoma chemoresistance through ARRB1-mediated signaling restoration.

Qiang Li, Jianglong Xu, Bin Ye, Peikan Jin, Diana Bee-Lan Ong, Kein Seong Mun, Xiuchao Geng, Yiping Tang, Kean Chang Phang.

Temozolomide (TMZ) resistance represents a primary cause of treatment failure and poor outcomes in glioblastoma (GBM). Exosome-mediated intercellular communication is increasingly recognized as a pivotal mechanism driving the dissemination of chemoresistance; however, the specific contribution of exosomal circular RNA cargos to this adaptive process remains elusive. This study systematically characterized the biological function of exosomal circ_0017636 in remodeling the TMZ-resistant microenvironment. We identified that circ_0017636 was significantly downregulated in TMZ-resistant tissues and correlated with poor prognosis. Mechanistically, circ_0017636 functions as a competing endogenous RNA that physically sponges miR-665 to de-repress Arrestin Beta 1 (ARRB1). Crucially, we isolated exosomes from sensitive cells and confirmed their identity via transmission electron microscopy (TEM) and marker analysis. Utilizing CD63-GFP fluorescent tracking, we visually demonstrated the efficient internalization of these vesicles by resistant recipient cells, confirming that circ_0017636 is physically packaged into these exosomes as a transferable cargo. Upon uptake, these circ_0017636-loaded exosomes effectively propagated chemosensitivity signals, significantly reducing the expression of the proliferation marker Ki-67 and the multidrug resistance protein P-glycoprotein (P-gp), thereby suppressing malignant phenotypes. Furthermore, vivo experiments confirmed that intratumoral delivery of circ_0017636-enriched exosomes significantly retarded xenograft tumor growth and overcame TMZ resistance. Collectively, this study elucidates a novel exosome-based communication axis, wherein circ_0017636 acts as a transferable tumor suppressor. Our findings suggest that leveraging exosomes as natural vehicles to deliver circ_0017636 represents a promising therapeutic strategy, while also indicating its potential as a diagnostic biomarker.

Keywords: ARRB1; Chemoresistance; Circular RNA; Exosomes; Glioblastoma

DOI: https://doi.org/10.1016/j.cellsig.2026.112432